Malignant melanoma is the most deadly form of skin cancer. It originates from melanocytic cells and can also arise at other body sites. Early diagnosis and appropriate medical care offer excellent prognosis with up to 5-year survival rate in more than 95% of all patients. However, long-term survival rate for metastatic melanoma patients remains at only 5%. Indeed, malignant melanoma is known for its notorious resistance to most current therapies and is characterized by both genetic and epigenetic alterations. In cutaneous melanoma (CM), genetic alterations have been implicated in drug resistance, yet the main cause of this resistance seems to be non-genetic in nature with a change in transcription programs within cell subpopulations. This change can adapt and escape targeted therapy and immunotherapy cytotoxic effects favoring relapse.

Because they are reversible in nature, epigenetic changes are a growing focus in cancer research aiming to prevent or revert the drug resistance with current therapies. As such, the field of epigenetic therapeutics is among the most active area of preclinical and clinical research with effects of many classes of epigenetic drugs being investigated. Here, we review the multiplicity of epigenetic alterations, mainly histone alterations and chromatin remodeling in both cutaneous and uveal melanomas, opening opportunities for further research in the field and providing clues to specifically control these modifications. We also discuss how epigenetic dysregulations may be exploited to achieve clinical benefits for the patients, the limitations of these therapies, and recent data exploring this potential through combinatorial epigenetic and traditional therapeutic approaches.

恶性黑色素瘤是最致命的皮肤癌。它起源于黑素细胞，也可能出现在身体其他部位。早期诊断和适当的医疗护理可提供良好的预后，所有患者的生存率高达 5 年以上。然而，转移性黑色素瘤患者的长期生存率仍仅为5%。事实上，恶性黑色素瘤以其对大多数当前疗法的耐药性而闻名，并且其特征是遗传和表观遗传改变。在皮肤黑色素瘤（CM）中，基因改变与耐药性有关，但这种耐药性的主要原因似乎是非遗传性的，即细胞亚群内转录程序的变化。这种变化可以适应并逃避有利于复发的靶向治疗和免疫治疗的细胞毒性作用。

由于表观遗传变化本质上是可逆的，因此它们越来越成为癌症研究的焦点，旨在通过当前疗法预防或恢复耐药性。因此，表观遗传治疗领域是临床前和临床研究最活跃的领域之一，许多类别的表观遗传药物的作用正在被研究。在这里，我们回顾了皮肤和葡萄膜黑色素瘤中表观遗传改变的多样性，主要是组蛋白改变和染色质重塑，为该领域的进一步研究提供了机会，并为专门控制这些修饰提供了线索。我们还讨论了如何利用表观遗传失调来为患者带来临床益处、这些疗法的局限性，以及通过组合表观遗传和传统治疗方法探索这种潜力的最新数据。